Network pharmacology and molecular simulations reveal multi-target neuroprotective potential of Rhamnolipid and...

Alzheimer's disease (AD), the primary cause of dementia and lacks potent therapeutic interventions. Natural biosurfactants containing Surfactin and Rhamnolipid, with neuroprotective capability and anti-inflammatory, extend favorable multi-target approaches.

This study examined the therapeutic potential of Surfactin and Rhamnolipid against Alzheimer's disease operating network pharmacology and molecular docking to manifest their multi-target pathways.

Network pharmacology was devoted to investigate Alzheimer's comparable targets of Rhamnolipid and Surfactin, observed by enrichment and network assay. Molecular docking and molecular dynamics simulations were then conducted to measure drug-target interactions and stability.

Network pharmacology recognized 87 overlapping targets of Rhamnolipid and Surfactin with Alzheimer's disease, with hub genes involving CASP3, SRC, CTNNB1, HSP90AA1 and STAT3. GO and KEGG assessment identified enhancement in pathways related to synaptic signaling, immune regulation, kinase activity, and neuroinflammation. Docking explorations illustrated Rhamnolipid exhibited strong binding affinities, distinctly with 1BYQ (-11.1 kcal/mol), 7SEO (-9.1 kcal/mol), and 2SRC (-9.0 kcal/mol) while Surfactin confirmed weaker interactions. Molecular dynamics simulations (MD) affirmed stable complexes, with the Rhamnolipid CASP3 complex revealing the highest conformational stability.

These findings indicate that biosurfactants, especially Rhamnolipid, exert neuroprotective effects against Alzheimer's disease through multi-target and multi-pathway functions. Their strong binding to crucial Alzheimer disease related proteins and stable interactions in dynamic simulations highlight their potential therapeutic agents, validating promote experimental validation.